Table 3.
Studies reported the treatments targeted by TLR4 in osteoporosis.
| Study | Study object | Intervention or treatment | Status of TLR4 | Effect on osteoblast or osteoclast | Associated genes or pathways | Main findings |
|---|---|---|---|---|---|---|
| Vijayan et al. (59), | Female Sprague-Dawley rats | Methionine | Inhibited | Inhibited osteoclast | TLR-4/MyD88/NF-κB pathway | Methionine inhibited the growth of osteoclast by suppressing TLR-4/MyD88/NF-κB pathway. |
| Tao et al. (60), | Osteoclasts and bone marrow-derived macrophages; ovariectomy-induced osteoporosis (OVX) mouse model | Dioscin | Inhibited | Promoted osteoblast | Inhibited TLR4/MyD88 pathway to decreased TRAF6 expression | Dioscin against OVX-induced bone loss by promoting osteoblastogenesis and suppressing osteoclastogenesis. |
| Zeng et al. (62), | RAW264.7 cells and mice | Artesunate | Inhibited | Inhibited osteoclastogenesis | Suppressed TLR4/TRAF6 and the PLCγ1-Ca2+-NFATc1 signaling cascade | Artesunate reduced the bone loss caused by gram-negative bacteria infection in a RANKL-independent manner. |
| Zhang et al. (63), | Ovariectomized rats | AEG-1 deletion | Inhibited | NA | Inhibited the TLR4/MyD88/NF-κB signaling cascade. | AEG-1 deletion improved bone remodeling in an osteoporosis animal model by inhibiting TLR4/MyD88/NF-κB pathway. |
| Lu et al. (64), | Bone marrow-derived macrophages | Patchouli Alcohol | Inhibited | Inhibited osteoclast | Downregulated TLR4/Myd88/TRAF6 via PXR and inhibited NF-κB signaling | Patchouli alcohol suppressed osteoclastogenesis by inhibiting RANKL-induced NF-κB signaling cascade. |
| Xie et al. (61), | MC3T3-E1 cells and bone marrow-derived macrophages | miR-1906 mimic | Inhibited | Inhibited osteoclast | Down-regulating the TLR4/MyD88/NF-kB cascade | miR-1906 mimic reduced bone loss of osteoporosis animal model by down-regulating the TLR4/MyD88/NF-kB pathway. |
| Yuan et al. (65), | Female ovariectomized C57/BL6 mice | Bacteroides vulgatus | Inhibited | NA | Inhibited TLR-4/p-NF-κB pathway | Bacteroides vulgatus reduced the colonic microbiota dysbiosis by down-regulating the colonic LPS/TLR-4/p-NF-κB pathway. |
TLR4, Toll-like receptor 4; BMSCs, Bone marrow mesenchymal stem cells; PXR, Pregnane X receptor; LPS, Lipopolysaccharide; ERK, Extracellular signal regulated kinase; MAPK, Mitogen-activated protein kinase; PI-3, Phosphatidylinositol-3; RANK, Receptor activator of NF-κB; RANKL,RANK ligand; TRAF, TNFR-associated factor; TRAP, Tartrate-resistant acid phosphatase; NF-κB, Nuclear factor kappa B; MyD88, Myeloid differentiation primary response gene 88.